Genetic Variant NM_005438.5:c.13T>C (chr11-65900327-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005438.5(FOSL1):c.13T>C(p.Phe5Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000918 in 1,088,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F5V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Consequence

FOSL1
NM_005438.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.66

Publications

0 publications found

Variant links:

Genes affected

FOSL1 (HGNC:13718): (FOS like 1, AP-1 transcription factor subunit) The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

FOSL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16188255).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005438.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOSL1	NM_005438.5	MANE Select	c.13T>C	p.Phe5Leu	missense	Exon 1 of 4	NP_005429.1	A0A0S2Z595
FOSL1	NM_001300844.2		c.13T>C	p.Phe5Leu	missense	Exon 1 of 3	NP_001287773.1	E9PPX2
FOSL1	NM_001300856.2		c.13T>C	p.Phe5Leu	missense	Exon 1 of 3	NP_001287785.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOSL1	ENST00000312562.7	TSL:1 MANE Select	c.13T>C	p.Phe5Leu	missense	Exon 1 of 4	ENSP00000310170.2	P15407-1
FOSL1	ENST00000531493.5	TSL:1	c.13T>C	p.Phe5Leu	missense	Exon 1 of 3	ENSP00000436276.1	E9PPX2
FOSL1	ENST00000913992.1		c.13T>C	p.Phe5Leu	missense	Exon 1 of 4	ENSP00000584051.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.18e-7

AC:

AN:

1088758

Hom.:

Cov.:

AF XY:

0.00000194

AC XY:

AN XY:

516286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22990

American (AMR)

AF:

0.00

AC:

AN:

8432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14424

East Asian (EAS)

AF:

0.00

AC:

AN:

26630

South Asian (SAS)

AF:

0.00

AC:

AN:

23050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3620

European-Non Finnish (NFE)

AF:

0.00000108

AC:

AN:

924180

Other (OTH)

AF:

0.00

AC:

AN:

43904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.040

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.41

M_CAP

Benign

0.052

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.1

PhyloP100

4.7

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.60

REVEL

Benign

0.16

Sift

Benign

0.48

Sift4G

Uncertain

0.031

Polyphen

0.0050

Vest4

0.39

MutPred

0.27

Gain of glycosylation at P8 (P = 0.2761)

MVP

0.78

MPC

0.12

ClinPred

0.80

GERP RS

4.4

PromoterAI

0.025

Neutral

(source)

Varity_R

0.096

gMVP

0.42

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over